Biomedical subjects

Frank L Powell

Publications and source records attributed to Frank L Powell.

9 recordsLinked to original sources

PubMed2006

A strategy for determining arterial blood gases on the summit of Mt. Everest.

BACKGROUND: Climbers on the summit of Mt. Everest are exposed to extreme hypoxia, and the physiological implications are of great interest. Inferences have been made from alveolar gas samples collected on the summit, but arterial blood samples would give critical information. We propose a plan to insert an arterial catheter at an altitude of 8000 m, take blood samples above this using an automatic sampler, store the samples in glass syringes in an ice-water slurry, and analyze them lower on the mountain 4 to 6 hours later. RESULTS: A preliminary design of the automatic sampler was successfully tested at the White Mountain Research Station (altitude 3800 m-4300 m). To determine how much the blood gases changed over a long period, rabbit blood was tonometered to give a gas composition close to that expected on the summit (PO2 4.0 kPa (30 mmHg), PCO2 1.3 kPa (10 mmHg), pH 7.7) and the blood gases were measured every 2 hours for 8 hours both at sea level and 3800 m. The mean changes were PO2 +0.3 to +0.4 kPa (+2 to +3 mmHg), PCO2 0 to +0.13 kPa (+1 mmHg), pH -0.02 to +0.04, base excess -0.7 to +1.2 mM. In practice the delay before analysis should not exceed 4 to 6 hours. The small paradoxical rise in PO2 is presumably caused mainly by contamination of the blood with air. CONCLUSION: We conclude that automatic arterial blood sampling at high altitude is technically feasible and that the changes in the blood gases over a period of several hours are acceptably small.

Altitude↗

PubMed2006

Lake Louise consensus methods for measuring the hypoxic ventilatory response.

The hypoxic ventilatory response (HVR) is the body's first line of defense against environmental hypoxia, for example, at high altitude. In acute hypoxia, the HVR is a reflex increase in ventilation in response to decreased arterial PO2, which is rapidly sensed by arterial chemoreceptors primarily in the carotid bodies. With sustained exposure to hypoxia, the HVR changes (8). For example, after 5 to 20 minutes of hypoxia, ventilation "rolls off' relative to the acute hypoxic response and this is called hypoxic ventilatory decline (HVD). With continuous hypoxia, for example during acclimatization to high altitude, ventilation increases above the level of the acute HVR with ventilatory acclimatization to hypoxia (VAH). The different time domains of the HVR raise many questions about the physiological mechanisms of oxygen sensing and the control of breathing. They also raise many issues about experimental methods to measure the HVR and comparing results between laboratories. At the 13th International Hypoxia Symposium, John Severinghaus proposed consensus methods for measuring the HVR in humans, and the discussion continued at the 14th International Hypoxia Symposium in Lake Louise. The goal of this report is to stimulate further discussion and experiments so we can adopt a "Lake Louise Consensus for Measuring the HVR" at the 15th International Hypoxia Symposium in 2007.

Acclimatization↗

PubMed2005

Effects of chronic hypoxia on MK-801-induced changes in the acute hypoxic ventilatory response.

Chronic hypoxia increases the sensitivity of the central nervous system to afferent input from carotid body chemoreceptors. We hypothesized that this process involves N-methyl-D-aspartate (NMDA) receptor-mediated mechanisms and predicted that chronic hypoxia would change the effect of the NMDA receptor blocker dizocilpine (MK-801) on the poikilocapnic hypoxic ventilatory response (HVR). Male Sprague-Dawley rats were studied before and after acclimatization to hypoxia (70 Torr inspiratory Po(2) for 9 days). We measured ventilation (VI) and the HVR before and after systemic MK-801 treatment (3 mg/kg ip). MK-801 resulted in a constant respiratory frequency (approximately 175 min(-1)) during acute exposure to 10% and 30% O(2) before and after acclimatization. MK-801 had no effect on tidal volume (VT) before acclimatization, but it significantly decreased Vt when the animals were breathing 10% O(2) after acclimatization. The net effect of MK-801 was to eliminate the O(2) sensitivity of Vi before (via changes in respiratory frequency) and after (via changes in VT) acclimatization. Hence, chronic hypoxia altered the effect of MK-801 on the acute HVR, primarily because of increased effects on Vt. This indicates that changes in NMDA receptor-mediated neurotransmission may be involved in ventilatory acclimatization to hypoxia. However, further experiments are necessary to determine the precise location of such plasticity in the central nervous system.

Acetamides↗

PubMed2005

Short-term isocapnic hypoxia and coagulation activation in patients with sleep apnea.

Hemostatic changes might contribute to the increased risk of cardiovascular and cerebrovascular events in patients with obstructive sleep apnea (OSA). We investigated the effect of a short-term isocapnic hypoxic challenge on coagulation activation markers thrombin/antithrombin III complexes (TAT) and D-dimer in OSA. Thirty-two OSA patients (mean age 48 +/- 11 years) inhaled a gas mixture containing 10% O(2) and 90% N(2) and further adjusted to yield pulse oximetry saturation of 80-85% for 5 minutes. Plasma levels of TAT and D-dimer were measured immediately before and immediately after the hypoxic challenge. The hypoxic challenge provoked a significant increase in TAT (p < 0.001) and in D-dimer (p = 0.037). Mean nocturnal oxygen saturation from the sleep recordings correlated with D-dimer increase (r = -0.37, p = 0.041). Also, OSA patients with a history of hypertensive parents had greater D-dimer increase in response to hypoxia than patients having normotensive parents (p = 0.035). Parental hypertension independently explained 15% of the variance in D-dimer increase after hypoxia (p = 0.035). Oxygen desaturation during sleep may predispose OSA patients, in particular those with a parental history of hypertension, to a hypercoagulable state providing one explanation for the increased risk of atherothrombotic events in this population.

Adult↗

PubMed2004

Breathing in thin air: acclimatization to altitude in ducks.

We measured ventilation (VI) and arterial blood gases in Pekin ducks during acclimatization to 3800 m altitude for 1-90 days. Four experimental series were conducted over 4 years using both natural altitude and a hypobaric chamber. PaCO2 decreased to 3.5 Torr, relative to the value measured during acute hypoxia after 1 day and remained at this level for up to 90 days. However, PaO2 did not increase. Arterial pH showed an unexpected metabolic alkalosis during the first hours at altitude but after 3 days, a metabolic acidosis partially compensated the respiratory alkalosis and pHa was constant thereafter. When normoxia was restored after hypoxia, PaCO2 was 5.5 Torr less than the original normoxic control value, but PaO2 was not increased. VI showed variable changes during acclimatization but if metabolic rate was constant in our study, as reported by others, then effective parabronchial V(VP) increased during acclimatization. Increased VP tends to restore PaO2 toward normoxic levels and decreases adverse effects of gas exchange limitation, which apparently increased during acclimatization in ducks.

Acclimatization↗

PubMed2004

Increased hypoxic ventilatory response during 8 weeks at 3800 m altitude.

Acclimatization to chronic hypoxia (CH) increases ventilation (V(I)) and the isocapnic hypoxic ventilatory response (HVR) over 2-14 days but hypoxic desensitization blunts the HVR after years of CH. We tested for hypoxic desensitization during the first 2 months of CH by studying five normal subjects at sea level (SL) and for 8 weeks at 3800 m (CH, PI(O(2)) approximately 90 Torr). We measured the isocapnic HVR (Delta V(I)/Delta Sa(O(2)) and tested for hypoxic ventilatory decline (HVD) by stepping Sa(O(2)) to 80% after 14 min at 90%. The HVR increased significantly after 2 days and remained significantly elevated for 8 weeks of CH. HVD was similar at SL and during 8 weeks of CH. Hence, hypoxic desensitization of the HVR does not occur after only 8 weeks of hypoxia and the increased HVR during this time does not involve changes in HVD.

Acclimatization↗

PubMed2004

Comparative physiology of lung complexity: implications for gas exchange.

Lungs evolved to increase diffusing capacity by compartmentalizing and reducing the size of individual gas exchange units. This increased the potential for gas exchange limitations from ventilation-perfusion heterogeneity. However, comparative studies on reptiles, birds, and mammals show that heterogeneity is independent of lung complexity.

Animals↗

PubMed2003

Persistence of the lactate paradox over 8 weeks at 3,800 m.

The arterial blood lactate [La] response to exercise increases in acute hypoxia, but returns to near the normoxic (sea level, SL) response after 2 to 5 weeks of altitude acclimatization. Recently, it has been suggested that this gradual return to the SL response in [La], known as the lactate paradox (LP), unexpectedly disappears after 8 to 9 weeks at altitude. We tested this idea by recording the [La] response to exercise every 2 weeks over 8 weeks at altitude. Five normal, fit SL-residents were studied at SL and 3,800 m (Pbar = 485 torr) in both normoxia (PIO2 = 150 torr) and hypoxia (PIO2 = 91 torr approximately air at 3,800 m). Arterial [La] and blood gas values were determined at rest and during cycle exercise at the same absolute workloads (0, 25, 50, 75, 90, and 100% of initial SL-VO2Max) and exercise duration (4, 4, 4, 2, 1.5, and 0.75 min, respectively) at each time point. [La] curves were elevated in acute hypoxia at SL (p < 0.01) and at 3,800 m fell progressively toward the SL-normoxic curve (p < 0.01). On the same days, [La] responses in acute normoxia showed essentially no changes over time and were similar to initial SL normoxic responses. We also measured arterial catecholamine levels at each load and found a close relationship to [La] over time, supporting a role for adrenergic influence on [La]. In summary, extending the time at this altitude to 8 weeks produced no evidence for reversal of the LP, consistent with prior data obtained over shorter periods of altitude residence.

Acclimatization↗

PubMed2002

Functional genomics and the comparative physiology of hypoxia.

Comparative physiology has proven a powerful approach to our understanding of how animals function under hypoxic conditions and to identifying potential adaptations to environmental oxygen levels. This review considers the potential for using a similar comparative approach with functional genomics to understand the genetic basis of such physiological processes and evolutionary adaptations. Comparative functional genomics is currently limited by genome data, which are available for only a few model organisms. However, comparative studies between model organisms of the same species having slightly different genomes (e.g., in-bred strains of laboratory rodents, transgenic mice, and consomic rats) demonstrate the types of results, as well as the analytical challenges, that are possible if comparative functional genomics is applied to more species. Results from wild and domestic animal studies suggest new models to investigate physiological and evolutionary responses to oxygen levels with functional genomics.

Animals↗